Project activities include a recently published study in which we evaluated, in aged surgically menopausal rhesus monkeys, the cognitive effects of four hormone therapy (HT) regimens designed to mimic treatments used clinically in women (Baxter et al., 2013). Whereas our earlier work had demonstrated that monthly acute estrogen injection benefits working memory capacities mediated by the prefrontal cortex in aged ovariectormized monkeys, HT in women has often failed to improve cognitive function in clinical studies. The possibility that this discrepancy reflects differences in the formulation and timing of HT regimens, however, has not been tested systematically. Notably, none of the four hormone treatments examined in our experiments produced any beneficial effects on cognition, despite documented efficacy measured by serum hormone levels. Consistent with these findings, and in contrast to our previous results in brains from animals provided cyclic estrogen administration, none of the HT regimens tested had any detectable effect on dendritic spine density in the monkey prefrontal cortex (Ohm et al., 2013). Continuing work on this project is testing whether there is a window of opportunity for protecting cognitive function after ovarian hormone decline, together with a variety of related questions concerning the brain morphometric influence of surgical menopause and hormone therapy.